Download Anticoagulation Management Policy

Anticoagulation Management Policy
PURPOSE:
To ensure the patients at Harris Regional Hospital and Swain Community Hospital who are on anticoagulation
therapy receive safe and effective care by a structured care management program.
POLICY:
All inpatients that have an active order for anticoagulation therapy will be followed by pharmacy. The
pharmacy service can be consulted to follow and adjust anticoagulation therapy based on patient specific
factors, lab values, and indication. Order for consult must have indication listed prior to pharmacy adjustments.
Pharmacy will follow attached nomograms as a guide when dosing anticoagulation therapy, which will be
reviewed annually through P&T. Pharmacists may use clinical judgment to supersede doses suggested by the
attached nomogram. All pharmacists dosing medications will have passed an initial competency exam provided
by the designated clinical lead on this program.
PROCEDURE:
Patients at Harris Regional Hospital and Swain Community Hospital who are prescribed anticoagulation will be
reviewed by the pharmacy clinical service. All patients on anticoagulation therapy will be tracked for
appropriate dosing based on renal function and we will assure that PT/INR is ordered prior to warfarin
initiation. Pharmacy can order baseline labs (CBC, CMP, or BMP) if not completed within the last 48 hours.
Patients on Coumadin must have an INR at least every 3 days. Pharmacists will work with providers on any
recommendations for improved patient care.
Providers can request pharmacy dosing consult along with providing the indication for anticoagulation. The
pharmacy consult will include medication dose adjustments as stated in guidelines, ordering of pertinent lab
work (PT/INR, CBC, BMP, or CMP), and patient education to include dietary considerations, drug interactions,
drug-disease interactions, and signs and symptoms of bleeding/bruising or thromboembolism. Any
considerations not directly discussed in the guideline for dosing anticoagulation will be discussed in
collaboration with the provider and the pharmacist. Clinical judgment should supersede the dosing nomogram.
At any time during the consult duration, if the drug regimen or medical condition changes, the pharmacist may
order labs more frequently. The provider can request for the consult at anytime during the patients stay by
writing an order for “Pharmacy to manage anticoagulation therapy,” or “Pharmacy to dose Coumadin,” or
similar wording.
Pharmacy will provide discharge counseling to anticoagulation patients on an as needed basis only or when
consulted by the provider to do so. Please see below for basic workflow:

Coumadin Order
a. Provider Dosing:
i. Pharmacy Assures Baseline INR; monitors for interactions
ii. Patient will need an INR ordered at a minimum of every 3 days
iii. Any significant interactions will be discussed with the provider
iv. Any INR > 4 will have medication held that day by pharmacist, any INR > 3 nurse will
call for critical lab.
b. Pharmacy Dosing:
i. Pharmacy assures baseline INR; monitors for interactions

ii. Must have indication listed for anticoagulation from provider
iii. Pharmacy will change dose daily based on MEC approved dosing
iv. Provider will be called if INR >4, or signs of bleeding (included but not limited to):
1. Hbg drop by more than 3 g/dL, Hbg less than 8 g/dL
2. Platelets less than 100,000
3. Positive Hemoccult
Injectable Anticoagulant:
a. Suggest a baseline Scr, H/H, Plt, and a minimum every 5 days thereafter
b. Renal dose per MEC approved dosing
c. Heparin will follow the specific guidelines on the heparin orderset
GENERAL GUIDELINES:
1. Obtain Baseline PT/INR, consider other labs per anticoagulant agent.
2. Determine indication and target INR for patient
3. Determine potential drug interactions and adjust starting dose if necessary
a. Make sure to ask patient about any over the counter medications
b. Check nurses note for stool or guaiac results, character of urine (clear yellow vs. red tinged, etc),
and diet for whether the patient is eating.
4. Usual starting dose will be 5mg. Standard time for warfarin administration is 1700 daily.
5. Consider factors that may increase warfarin sensitivity and adjust initial starting dose
a. See guidelines for a list of factors affecting Coumadin sensitivity/resistance
b. These may suggest a lower Coumadin starting dose such as 2.5 mg daily.
c. For young and healthy patients consider starting 5 mg to 10mg daily.
6. If patient has been on Coumadin before restart at this dose initially.
a. Unless admission INR is not in range without an identifiable cause
b. Presence of factors that may affect INR while inpatient may suggest a change
7. Do not initiate warfarin and contact the physician if patient is on an epidural infusion
8. The second day’s dose is based on response to the first dose. The prothrombin time would normally be
expected to be minimal on day two. If there is a substantial prothrombin time increase on day 2, there
would in turn need to be a substantial decrease in warfarin, otherwise, starting dose can be repeated per
guidelines.
9. On day three, there may be movement of prothrombin time toward therapeutic range. If not, consider
increasing dose from starting dose. If prothrombin time is supratherapeutic, consider a lower dose. On
day three you have not seen the maximal effect of the first two doses.
10. By day five, if patient is still subtherapeutic, you should evaluate for lab error, missed doses, drug
interactions, dietary or pharmaceutical vitamin K intake, and active disease states. True warfarin
resistance does occur, but is quite rare.
11. Remember, the patient must be bridged with an injectable anticoagulant for a minimum of 5 days AND
while the INR is >2 for at least 24 hours.
12. Anticoagulation may be seen within 24 hours due to the sensitivity of the INR to factor VII (shortest half
life), but peak anticoagulation is delayed for 72-96 hours due to Factor II inhibition.
Anticoagulation Dosing Guidelines:
1. Factors Identifying Warfarin Sensitive Patients (consider lower starting
dose):
Increased INR Response
Baseline INR ≥ 1.5
Age > 65
Actual body weight < 45 kg or actual <
ideal
Malnourished/ NPO >3 days
Hypoalbuminemia <2 g/dl
Prolonged diarrhea (>3 days)
Significant drug interactions
Recent alcohol binge
Increased Bleeding Risk
Surgery within past 2 weeks
Thrombocytopenia: platelet
<75 K/uL
Significant hepatic disease:
cirrhosis or total bilirubin.>2.4
mg/dL
Alcohol abuse history
End stage renal disease
GI bleed within past 30 days
Intracranial bleed within past
30 days
Medications:
Aspirin
NSAIDS
Clopidogrel
Ticlodipine
Hepatic insufficiency/Active Liver disease Thromocytopenia
Fever (>3 days)
Decompensated heart failure or Acute HF
exacerbation
Clinical hyperthyroidism
2. Factors identifying possible Warfarin Resistance (consider higher initial dose):






Weight >100kg
African American patients
Clinical Hypothyroidism
Medications (see chart on concomitant medications and interactions)
Heavy smoker
Chronic alcohol use
3. Medications Altering Warfarin Pharmacokinetics and Pharmacodynamics (non inclusive list)
INCREASED WARFARIN EFFECT
Acetaminophen (high dose multiple
days)
Alcohol (acute ingestion)
Aminosalicylic acid
Allopurinol
amiodarone
aspirin
cimetideine
ciprofloxacin
DECREASED WARFARIN EFFECT
Alcohol (chronic ingestion)
Barbituates
carbamazepine
cholestyramine
dicloxacillin
griseofulvin
nafcillin
phenytoin
clarithromycin
Disulfiram
erythromycin
Rifampin
sucralfate
Vitamin K (tube feeds and
supplements)
Fluconazole
Itraconazole
Isoniazid (600mg/day)
levothyroxine
metronidazole
omeparazole
Phenytoin (chronic)
Quinidine
sulfonylurea
Tamoxifen
Tetracycline
TMP/SMX
4. Warfarin Initiation for Naïve Patients (Target INR 2-3):
DAY OF THERAPY
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
INR
Dose
<1.5
1.5-1.9
2.0-2.5
>2.5
<1.5
1.5-1.9
2.0-3.0
>3.0
<1.5
1.5-1.9
2.0-3.0
>3.0
<1.5
1.5-1.9
2.0-3.0
>3.0
<1.5
1.5-1.9
2.0-3.0
>3.0
5 mg
5mg
2.5mg
1-2.5mg
HOLD
5- 10mg
2.5-5mg
0-2.5mg
HOLD
10mg
5- 7.5mg
0-5 mg
HOLD
10 mg
7.5 mg- 10 mg
0- 5 mg
HOLD
7.5- 12.5 mg
5-10 mg
0-7.5 mg
HOLD
5. Warfarin Initiation for Naïve Patients starting dose 2.5 mg- 10mg (Target INR 2-3) :
DAY OF THERAPY
INR
Dose
Day 1
Day 2
Day 3
Day 4
Day 5
<1.5
1.5-1.9
2.0-2.5
>2.5
<1.5
1.5-1.9
2.0-2.5
>2.5
<1.5
1.5-1.9
2.0-2.5
>2.5
<1.5
1.5-1.9
2.0-2.5
>2.5
2.5 -10 mg
No dosage change
Decrease dose by 25-50%
Decrease dose by 50-75%
Hold next dose
Increase dose by 0-25%
No dosage change
Decrease dose by 25-50%
Decrease dose by 50% or hold one dose
Increase dose by 0-25%
No dosage change or increase by 10-25%
Decrease dose by 0-25%
Decrease dose by 50% or hold one dose
Increase dose by 25%
Increase dose by 0-25%
No dosage change or decrease 10-25%
Decrease dose by 25-50%
6. Warfarin Initiation for Naïve Patients (Target INR 2.5-3.5)
DAY OF THERAPY
Day 1
Day 2
Day 3
Day 4
Day 5
INR
Dose
<1.5
1.5-1.9
>2.0
<1.5
1.5-1.9
2.0-2.4
>2.5
<1.6
1.6-2.3
2.4- 3.0
3.1-3.4
>3.5
<1.5
1.5-1.9
2.0-2.5
2.5-3.5
3.6-3.9
4- 4.4
>/=4.5
5 mg
5mg
0-2.5mg
HOLD
5- 7.5mg
5-7.5 mg
0-2.5mg
HOLD
7.5-10mg
5- 7.5mg
0-7.5 mg
0-2.5mg
HOLD
7.5-10 mg
7.5- 10 mg
2.5-7.5 mg
2.5-5 mg
0-2.5 mg
0-1 mg
HOLD
INR
INR not within range, but
<5
No clinically significant
bleeding
Description



Monitor INR every 24 hours until INR is stable
Reduce or skip warfarin dose
Resume at a lower dose when INR therapeutic (no reduction may be
necessary if close to INR goal).
INR = 5-9
No clinically significant
bleeding

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

Monitor INR every 24 hours until INR is stable
Hold 1-2 doses of warfarin
Resume warfarin at a lower dose when INR therapeutic
Vitamin K not routinely recommended if no evidence of bleeding
INR = 5.0-9.0
No clinically significant
bleeding



Give phytonadione 1mg – 5mg PO once (reversal in 24 hours)
If INR remains high after 24 hours, repeat initial PO phytonadione dose
If INR remains high at 24 hours, may give an phytonadione 2.5 mg PO
once or phytonadione 1mg IV in 50 mL of NS by slow infusion over 60
minutes (reversal 6-12 hours)



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

Repeat INR initially, monitor INR every 24 hours until INR is stable
Hold warfarin only to restart when clinically appropriate
Give Vitamin K 2.5mg- 5mg PO once, even if not bleeding
Resume warfarin at lower dose when INR therapeutic
Hold warfarin only to restart when clinically appropriate
Mix phytonadione 10mg IV in 50mL of normal saline and administer as a
slow IV infusion over 60 minutes—may repeat every 12 hours if
indicated.
Consider use of FFP or Kcentra, depending on clinical urgency
Monitor INR every 2 hours
RAPID REVERSAL
NEEDED FOR SURGERY
INR > 10
No clinically significant
bleeding
Life-threatening bleed
OR
Serious warfarin
overdose


7. How to
Manage
Elevated
INRs or
bleeding in
Patients
receiving
Warfarin:
8. Recommendations for Bridge Therapy


For patients with stable therapeutic INRs presenting with a single subtherapeutic INR value, no bridge therapy
with LMWH or heparin recommended
Acute DVT/PE Management:
o In patients with acute DVT of the leg, we recommend early initiation of VKA (eg, same day as parenteral
therapy is started) over delayed initiation, and continuation of parenteral anticoagulation for a minimum
of 5 days and until the international normalized ratio (INR) is 2.0 or above for at least 24 h
o

In patients with acute PE, we recommend early initiation of VKA (eg, same day as parenteral therapy is
started) over delayed initiation, and continuation of parenteral anticoagulation for a minimum of 5 days
and until the INR is 2.0 or above for at least 24 h
Perioperative Management:
o In patients with a mechanical heart valve, atrial fibrillation, or VTE at high risk for thromboembolism, we
suggest bridging anticoagulation instead of no bridging during interruption of VKA therapy
o In patients with a mechanical heart valve, atrial fibrillation, or VTE at low risk for thromboembolism, we
suggest no bridging instead of bridging anticoagulation during interruption of VKA therapy
9. Warfarin Indications
Thrombophilia with Thromboembolic Event
Antiphospholipid Syndrome
2.5 (2-3)
Chronic
Homozygous Factor V Leiden
2.5 (2-3)
Chronic
Deficiency of Protein C, S or
2.5 (2-3)
Chronic
Anti-Thrombin
Atrial Fibrillation (AF)/ Atrial Flutter
CHADS2 = 0; Low stroke risk
None
May choose aspirin 75-325 mg
daily
CHADS2 = 1; Intermediate
2.5 (2-3)
Chronic
CI anticoagulation: aspirin 75stroke risk
325 mg and clopidogrel 75 mg
daily
CHADS2 ≥ 2; High stroke risk
2.5 (2-3)
Chronic
CI anticoagulation: aspirin 75325 mg and clopidogrel 75 mg
daily
With mitral stenosis
2.5 (2-3)
Chronic
CI anticoagulation: aspirin 75325 mg and clopidogrel 75 mg
daily
With stable CAD
2.5 (2-3)
Chronic
No aspirin needed
Pre-cardioversion (AF or flutter 2.5 (2-3)
3 weeks
>48 hours)
Post-cardioversion (in NSR)
2.5 (2-3)
4 weeks
Non-cardioembolic stroke or
TIA
Cardioembolic stroke or TIA
-With warfarin CI
-With cerebral venous sinus
thrombosis
- With patent foramen ovale
- With other indication for
anticoagulation (VTE, AF)
Mitral prosthetic
Aortic prosthetic
Mechanical valve (low bleeding
risk)
None
Ischemic Stroke
Chronic
Use antiplatelet therapy
None
2.5 (2-3)
Chronic
3-6 months
Aspirin 81-325 mg daily
None
2.5 (2-3)
Chronic
Chronic
Use antiplatelet therapy
Heart Valves
3.0 (2.5-3.5
3 months, then use aspirin
None
Aspirin 50-100mg daily
None
Aspirin 50-100mg daily
Aortic (caged ball or caged
disk)
Aortic bileaflet or Medtronic
Hall tilting disk in NSR with nk
LA size
Mitral bileaflet, tilting disk,
caged ball, or caged disk
VTE- transient risk factor
VTE- unprovoked
VTE- second episode
3.0 (2.5-3.5)
Chronic
2.5 (2-3)
Chronic
3.0 (2.5-3.5)
Chronic
VTE Treatment
2.5 (2-3)
3 months
2.5 (2-3)
At least 3 months- re-evaluate risk/benefit after 3
months treatment
2.5 (2-3)
Chronic
10. Evaluating bleeding risk versus stroke risk:
CHADS2 Score to Estimate Stroke Risk in Atrial Fibrillation
Score
Risk of Thromboembolic Event
Congestive heart failure (1 point)
0
1.9%
Hypertension (1 point)
1
2.8%
Age >/= 75 years (1 point)
2
4.0%
Diabetes (1 point)
3
5.9%
Stroke (2 points)
4
8.5%
5
12.5%
6
18.2%
Hepatic or Renal disease
Ethanal abuse
Malignancy
Older (Age >75 years old)
Reduced platelets
Rebleeding risk
Hypertension (uncontrolled)
Anemia
Genetic factors (CYP2C9)
Excessive fall risk
Stroke
HEMMORR2HAGES Bleeding Risk
Score
0
1
2
3
4
5+
Bleed Rate
1.9
2.5
5.3
8.4
10.4
12.3
11. Comparison of NOAC medications:
Class
Dosing in
non valvular
A.fib
Apixiban
Direct selective factor Xa
inhibitor
5mg PO BID
*If 2 of following: Age
>=80 years, <60 kg, or Scr
> 1.5 give 2.5mg PO BID
Dabigatran
Direct thrombin
inhibitor
150mg PO BID
*CrCl 15-30 mL/min
75mg PO BID
*CrCl <15 -Avoid
Edoxaban
Direct factor Xa
inhibitor
60mg PO daily
*CrCl 15-50 mL/min
reduce to 30mg PO
daily
Rivaroxaban
Direct factor Xa inhibitor
20mg PO daily
*CrCl 15-50 mL/min give
15mg PO daily
*CrCl <15 - Avoid
*CrCl >95mL/minAvoid use
CrCl <15 mL/minAvoid
>60 kg: 60mg PO daily
<=60kg: 30 mg PO
daily
*Must treat with
parenteral
anticoagulant for 5-10
days first.
*CrCl 15-50 mL/min
reduce to 30mg PO
daily
Dosing
PE/DVT
Treatment
10mg PO BID x 7 days,
5mg PO BID x 6 mths
150mg PO BID
*Must treat with
parenteral
anticoagulant for 5-10
days first.
*CrCl<30 mL/min Avoid
DVT
prophylaxis
Half-life
Elimination
2.5 mg PO BID
8-13 hours
25% renal, 75% fecal
150mg-220mg PO
daily.
12-14 hours
80% renal
9-11 hours
33% renal, 66% fecal
Major Drug
Drug
Interactions
Check dose with strong
CYP3A4 inhibitor and Pglycoprotein inhibitor
Check dose changes
with P-glycoprotein
inhibitors
Check dose with Pglycoprotein inhibitors
and inducers
15mg PO BID x 21 days,
then 20mg PO daily x 6
months
CrCl<30 mL/min-Avoid
10mg PO daily
CrCl <30 mL/min- Avoid
7-13 hours
67% renal (half inactive
drug), 33% fecal
Check dose with strong
CYP3A4 inhibitor and Pglycoprotein inhibitor
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Pharm. 2013;70:S12-20.
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27.
4. Rivaroxaban, Apixiban, Dagibatran, Edoxaban. Clinical Pharmacology. Accessed 10/15/15:
http://www.clinicalpharmacology-ip.com.
5. Bridging Anticoagulation. Uptodate. Accessed 11/5/15.
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2005:373-413
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